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81.
Bruce E. Maryanoff Michael J. Costanzo Ricahrd P. Shank James J. Schupsky Marta E. Ortegon Jeffry L. Vaught 《Bioorganic & medicinal chemistry letters》1993,3(12):2653-2656
Exploration structure-activity relationships surrounding the clinically effective antiepileptic drug topiramate (1) led to a series of potent anticonvulsants with a 4,5-cyclic sulfate or 4,5-cycli sulfite functionality. Key derivative 2 (RWJ-37947) is ca. 8 times more potent than topiramate in mice; it also features a long duration of action and a very favorable neurotoxicity index. 相似文献
82.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
83.
Roberto de la Herrán Miguel Hermida Juan Andres Rubiolo Jèssica Gómez-Garrido Fernando Cruz Francisca Robles Rafael Navajas-Pérez Andres Blanco Paula Rodriguez Villamayor Dorinda Torres Pablo Sánchez-Quinteiro Daniel Ramirez Maria Esther Rodríguez Alberto Arias-Pérez Ismael Cross Neil Duncan Teresa Martínez-Peña Ana Riaza Adrian Millán M. Cristina De Rosa Davide Pirolli Marta Gut Carmen Bouza Diego Robledo Laureana Rebordinos Tyler Alioto Carmelo Ruíz-Rejón Paulino Martínez 《Molecular ecology resources》2023,23(4):886-904
Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis. 相似文献
84.
Przybyłowski J Kowalski D Widłak H Kowalska K Maślany P 《Polski tygodnik lekarski (Warsaw, Poland : 1960)》1995,50(1-35):794-796
In 66 patients with peptic ulcer (11 with gastric ulcer, 55 with duodenal ulcer, 19 women, 47 men) the serum concentrations of prolactin, dehydrocholic acid and gastrin were determined. The studies were repeated after treatment with ranitidine: in 50 patients after three weeks and in 40 patients after another 30 days. During the first period ranitidine 2 x 150 mg was administered, while during the second period the dose was 1 x 150 mg. The results were compared with those obtained from 120 healthy subjects. Before starting the treatment prolactin levels were significantly higher than those in the control group. During the treatment a significant decrease of the levels was observed. Similar changes of prolactin concentrations were found in the group of 39 men with duodenal ulcer isolated from the studied patients, who were compared with a group of 50 healthy men. It was not found that the development of peptic ulcer and the treatment with ranitidine exerted and effect on the changes of gastrin and dehydrocholic acid concentrations. 相似文献
85.
86.
87.
Ruth Meléndez Enrique Meléndez-Hevia Marta Cascante 《Journal of molecular evolution》1997,45(4):446-455
Optimization of molecular design in cellular metabolism is a necessary condition for guaranteeing a good structure–function
relationship. We have studied this feature in the design of glycogen by means of the mathematical model previously presented
that describes glycogen structure and its optimization function [Meléndez-Hevia et al. (1993), Biochem J 295: 477–483]. Our
results demonstrate that the structure of cellular glycogen is in good agreement with these principles. Because the stored
glucose in glycogen must be ready to be used at any phase of its synthesis or degradation, the full optimization of glycogen
structure must also imply the optimization of every intermediate stage in its formation. This case can be viewed as a molecular
instance of the eye problem, a classical paradigm of natural selection which states that every step in the evolutionary formation of a functional structure
must be functional. The glycogen molecule has a highly optimized structure for its metabolic function, but the optimization
of the full molecule has meaning and can be understood only by taking into account the optimization of each intermediate stage
in its formation.
Received: 23 October 1996 / Accepted: 21 April 1997 相似文献
88.
Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen 总被引:3,自引:0,他引:3
Pablos Marta I.; Reiter Russel J.; Chuang Jin-Ing; Ortiz Genaro G.; Guerrero Juan M.; Sewerynek Ewa; Agapito Maria T.; Melchiorri Daniela; Lawrence Richard; Deneke Susan M. 《Journal of applied physiology》1997,83(2):354-358
Pablos, Marta I., Russel J. Reiter, Jin-Ing Chuang, GenaroG. Ortiz, Juan M. Guerrero, Ewa Sewerynek, Maria T. Agapito, DanielaMelchiorri, Richard Lawrence, and Susan M. Deneke. Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen. J. Appl.Physiol. 83(2): 354-358, 1997.Hyperbaric oxygenexposure rapidly induces lipid peroxidation and cellular damage in avariety of organs. In this study, we demonstrate that the exposure ofrats to 4 atmospheres of 100% oxygen for 90 min is associated withincreased levels of lipid peroxidation products [malonaldehyde(MDA) and 4-hydroxyalkenals (4-HDA)] and withchanges in the activities of two antioxidative enzymes[glutathione peroxidase (GPX) and glutathione reductase (GR)], as well as in the glutathione status in the lungs and in the brain. Products of lipid peroxidation increased after hyperbaric hyperoxia, both GPX and GR activities were decreased, and levels oftotal glutathione (reduced+oxidized) and glutathione disulfide (oxidized glutathione) increased in both lung and brain areas (cerebralcortex, hippocampus, hypothalamus, striatum, and cerebellum) but not inliver. When animals were injected with melatonin (10 mg/kg) immediatelybefore the 90-min hyperbaric oxygen exposure, all measurements ofoxidative damage were prevented and were similar to those in untreatedcontrol animals. Melatonin's actions may be related to a variety ofmechanisms, some of which remain to be identified, including itsability to directly scavenge free radicals and its induction ofantioxidative enzymes via specific melatonin receptors. 相似文献
89.
Paweł Kafarski Barbara Lejczak Roman Tyka Lucyna Koba Elżbieta Pliszczak Piotr Wieczorek 《Journal of Plant Growth Regulation》1995,14(4):199-203
A series of phosphonic, phosphinic, and phosphonous acid analogues of phenylglycine and phenylalanine was synthesized and tested as herbicides against Lepidium sativum and Cucumis sativus. Aminobenzylphosphonic acids exhibited notable herbicidal activity and thus represent a group of the most active herbicides found among aminophosphonic acids. 相似文献
90.
Two series of amino-modified silicate gels prepared by sol-gel processing were used to absorb Cu(II), Ni(II), Co(II), Mn(II) and Cr(III) from aqueous solutions. These easily prepared sorbents with various content of primary amino groups in series (A) or primary and secondary amino groups in series (AA) have reasonable stability. The gel composition, time and concentration dependence of the uptake of the metal ions by these materials were studied systematically. These materials would be further used as supports to disperse catalytically active phases by conventional wet chemical procedures. Apart from this they demonstrate potential for the preconcentration aid for transition metal analysis. 相似文献